Azacitidine-Gemtuzumab Combo Effective in Good-Risk AML

CHICAGO – Patients with good-risk acute myeloid leukemia might benefit from a combination of azacitidine and gemtuzumab followed by azacitidine maintenance – if gemtuzumab were available in the United States.

The combination produced a 44% complete remission (CR) rate in 79 patients aged 60-69 years with acute myeloid leukemia (AML) or a Zubrod performance score of 0 or 1, reported investigators from the Southwest Oncology Group (SWOG) at the annual meeting of the American Society of Clinical Oncology

Median overall survival was 11 months and median relapse-free survival was 8 months among patients who achieved a CR or CR with complete remission in marrow but without recovery of neutrophil or platelet counts (CRi), said Dr. Sucha Nand, professor of medicine at Loyola University in Maywood, Ill.

The induction regimen is safe enough to be provided in an outpatient setting, noted Dr. Nand, who presented the data on behalf of coinvestigators in the Southwest Oncology Group (SWOG) S0703 protocol.

"In our opinion, these results are sufficiently encouraging to warrant further studies of this approach. Continuation of azacitidine therapy after completion of this regimen may prove to be of additional benefit," he said.

The problem is that gemtuzumab ozogamicin (Mylotarg) is no longer on the market, having been voluntarily withdrawn by Pfizer in 2010 after questions arose about its efficacy and safety.

"If gemtuzumab were suddenly to become available, I think this is a reasonable treatment regimen," commented Dr. Bruno Medeiros of Stanford (Calif.) University, the invited discussant.

The combination of gemtuzumab and azacitidine (Vidaza) produces CR rates, response duration, and survival similar to that of other AML regimens, with a lower incidence of early death and manageable toxicities that allow it to be delivered in an outpatient setting, said Dr. Medeiros.

Age has a significant effect on outcomes in patients with AML, with the proportion of patients in one study (Blood 2006;107:3481-5) who achieved a complete response to therapy declining from 65% for patients under age 56 years, to 33% for those older than 75 years. In the same study, the proportion of patients who died within 30 days of study entry rose from 2.7% of the youngest patients, to 31.6% of the oldest, Dr. Nand noted.

The SWOG investigators examined the combination to see whether previously untreated patients with non-M3 (acute promyelocytic leukemia) AML with a favorable risk factor profile could benefit in terms of the safety profile, efficacy, or both.

Patients with high white blood cell counts (10,000 mcL of higher) were pretreated with hydroxyurea 1,500 mg orally twice day, then started on induction with azacitidine 75 mg.m² subcutaneously or intravenously on days 1-7, followed by gemtuzumab 3 mg/m² on day 8. The induction regimen was repeated if bone marrow showed residual leukemia on day 14.

Patients then underwent consolidation with one treatment of azacitidine and gemtuzumab in the same doses, followed by azacitidine maintenance given every 28 days for up to four cycles.

Of the 79 patients available for evaluation, 75 completed planned treatment. One patient died, one discontinued because of toxicities, and two discontinued for reasons not related to the protocol.

A total of 35 patients achieved either a CR or a CRi, 1 had a partial response, 40 had resistant disease, and 1 had inadequate data for assessment.

Two patients had complete responses that occurred after being removed from the study on day 28 for residual disease. Both of these patients had had significant reduction in marrow blast count, and were continued on azacitidine alone.

At a median of 8.3 months follow-up, 35 patients remained relapse free. At a median of 11 months follow-up, 53 of the 79 patients had died.

The study was supported by the National Institutes of Health. Dr. Nand disclosed ties with Celgene. Dr. Medeiros disclosed ties with Millennium, Celgene, and Novartis.

CHICAGO – Patients with good-risk acute myeloid leukemia might benefit from a combination of azacitidine and gemtuzumab followed by azacitidine maintenance – if gemtuzumab were available in the United States.

The combination produced a 44% complete remission (CR) rate in 79 patients aged 60-69 years with acute myeloid leukemia (AML) or a Zubrod performance score of 0 or 1, reported investigators from the Southwest Oncology Group (SWOG) at the annual meeting of the American Society of Clinical Oncology

Median overall survival was 11 months and median relapse-free survival was 8 months among patients who achieved a CR or CR with complete remission in marrow but without recovery of neutrophil or platelet counts (CRi), said Dr. Sucha Nand, professor of medicine at Loyola University in Maywood, Ill.

The induction regimen is safe enough to be provided in an outpatient setting, noted Dr. Nand, who presented the data on behalf of coinvestigators in the Southwest Oncology Group (SWOG) S0703 protocol.

"In our opinion, these results are sufficiently encouraging to warrant further studies of this approach. Continuation of azacitidine therapy after completion of this regimen may prove to be of additional benefit," he said.

The problem is that gemtuzumab ozogamicin (Mylotarg) is no longer on the market, having been voluntarily withdrawn by Pfizer in 2010 after questions arose about its efficacy and safety.

"If gemtuzumab were suddenly to become available, I think this is a reasonable treatment regimen," commented Dr. Bruno Medeiros of Stanford (Calif.) University, the invited discussant.

The combination of gemtuzumab and azacitidine (Vidaza) produces CR rates, response duration, and survival similar to that of other AML regimens, with a lower incidence of early death and manageable toxicities that allow it to be delivered in an outpatient setting, said Dr. Medeiros.

Age has a significant effect on outcomes in patients with AML, with the proportion of patients in one study (Blood 2006;107:3481-5) who achieved a complete response to therapy declining from 65% for patients under age 56 years, to 33% for those older than 75 years. In the same study, the proportion of patients who died within 30 days of study entry rose from 2.7% of the youngest patients, to 31.6% of the oldest, Dr. Nand noted.

The SWOG investigators examined the combination to see whether previously untreated patients with non-M3 (acute promyelocytic leukemia) AML with a favorable risk factor profile could benefit in terms of the safety profile, efficacy, or both.

Patients with high white blood cell counts (10,000 mcL of higher) were pretreated with hydroxyurea 1,500 mg orally twice day, then started on induction with azacitidine 75 mg.m² subcutaneously or intravenously on days 1-7, followed by gemtuzumab 3 mg/m² on day 8. The induction regimen was repeated if bone marrow showed residual leukemia on day 14.

Patients then underwent consolidation with one treatment of azacitidine and gemtuzumab in the same doses, followed by azacitidine maintenance given every 28 days for up to four cycles.

Of the 79 patients available for evaluation, 75 completed planned treatment. One patient died, one discontinued because of toxicities, and two discontinued for reasons not related to the protocol.

A total of 35 patients achieved either a CR or a CRi, 1 had a partial response, 40 had resistant disease, and 1 had inadequate data for assessment.

Two patients had complete responses that occurred after being removed from the study on day 28 for residual disease. Both of these patients had had significant reduction in marrow blast count, and were continued on azacitidine alone.

At a median of 8.3 months follow-up, 35 patients remained relapse free. At a median of 11 months follow-up, 53 of the 79 patients had died.

The study was supported by the National Institutes of Health. Dr. Nand disclosed ties with Celgene. Dr. Medeiros disclosed ties with Millennium, Celgene, and Novartis.

CHICAGO – Patients with good-risk acute myeloid leukemia might benefit from a combination of azacitidine and gemtuzumab followed by azacitidine maintenance – if gemtuzumab were available in the United States.

The combination produced a 44% complete remission (CR) rate in 79 patients aged 60-69 years with acute myeloid leukemia (AML) or a Zubrod performance score of 0 or 1, reported investigators from the Southwest Oncology Group (SWOG) at the annual meeting of the American Society of Clinical Oncology

Median overall survival was 11 months and median relapse-free survival was 8 months among patients who achieved a CR or CR with complete remission in marrow but without recovery of neutrophil or platelet counts (CRi), said Dr. Sucha Nand, professor of medicine at Loyola University in Maywood, Ill.

The induction regimen is safe enough to be provided in an outpatient setting, noted Dr. Nand, who presented the data on behalf of coinvestigators in the Southwest Oncology Group (SWOG) S0703 protocol.

"In our opinion, these results are sufficiently encouraging to warrant further studies of this approach. Continuation of azacitidine therapy after completion of this regimen may prove to be of additional benefit," he said.

The problem is that gemtuzumab ozogamicin (Mylotarg) is no longer on the market, having been voluntarily withdrawn by Pfizer in 2010 after questions arose about its efficacy and safety.

"If gemtuzumab were suddenly to become available, I think this is a reasonable treatment regimen," commented Dr. Bruno Medeiros of Stanford (Calif.) University, the invited discussant.

The combination of gemtuzumab and azacitidine (Vidaza) produces CR rates, response duration, and survival similar to that of other AML regimens, with a lower incidence of early death and manageable toxicities that allow it to be delivered in an outpatient setting, said Dr. Medeiros.

Age has a significant effect on outcomes in patients with AML, with the proportion of patients in one study (Blood 2006;107:3481-5) who achieved a complete response to therapy declining from 65% for patients under age 56 years, to 33% for those older than 75 years. In the same study, the proportion of patients who died within 30 days of study entry rose from 2.7% of the youngest patients, to 31.6% of the oldest, Dr. Nand noted.

The SWOG investigators examined the combination to see whether previously untreated patients with non-M3 (acute promyelocytic leukemia) AML with a favorable risk factor profile could benefit in terms of the safety profile, efficacy, or both.

Patients with high white blood cell counts (10,000 mcL of higher) were pretreated with hydroxyurea 1,500 mg orally twice day, then started on induction with azacitidine 75 mg.m² subcutaneously or intravenously on days 1-7, followed by gemtuzumab 3 mg/m² on day 8. The induction regimen was repeated if bone marrow showed residual leukemia on day 14.

Patients then underwent consolidation with one treatment of azacitidine and gemtuzumab in the same doses, followed by azacitidine maintenance given every 28 days for up to four cycles.

Of the 79 patients available for evaluation, 75 completed planned treatment. One patient died, one discontinued because of toxicities, and two discontinued for reasons not related to the protocol.

A total of 35 patients achieved either a CR or a CRi, 1 had a partial response, 40 had resistant disease, and 1 had inadequate data for assessment.

Two patients had complete responses that occurred after being removed from the study on day 28 for residual disease. Both of these patients had had significant reduction in marrow blast count, and were continued on azacitidine alone.

At a median of 8.3 months follow-up, 35 patients remained relapse free. At a median of 11 months follow-up, 53 of the 79 patients had died.

The study was supported by the National Institutes of Health. Dr. Nand disclosed ties with Celgene. Dr. Medeiros disclosed ties with Millennium, Celgene, and Novartis.